Drawing up a blueprint for a synthetic bacterium.

Last year we chose synthetic biology, in particular the creation of a synthetic, live organism with a minimal genome, as a method to watch. Although that task was not achieved in 2009, significant strides towards this ultimate goal were nevertheless reported.

One of the many aims of the broad field of synthetic biology is to harness biological processes to address such global challenges as producing biofuels, synthesizing complex pharmaceuticals and cleaning up polluted environments. Another major objective is to grasp the elusive nature of what is fundamentally required for cellular life.

Researchers at the J. Craig Venter Institute have made it a long-term goal to design a synthetic organism containing the bare minimum of genes required for life, both for practical applications and for understanding basic biology. This necessitated the development of new methods to synthesize and assemble genomes. In 2008, Venter and colleagues used in vitro recombination to join small synthetic fragments into larger DNA strands, but they needed to move into yeast for the final recombination step to assemble the 583-kb genome of Mycoplasma genitalium (Science 319, 1215–1220, 2008). In 2009, they pushed this approach further, demonstrating all–in vitro assembly of the M. genitalium genome (Nat. Methods 6, 343–345, 2009). This not only streamlines the method but also circumvents problems of incompatibility between the synthetic genome and the host.

Also in 2009, Venter and colleagues showed that they could manipulate the cloned Mycoplasma mycoides genome in yeast before transplanting it into Mycoplasma capricolum (Science 325, 1693–1696, 2009). Besides providing a useful approach for manipulating genetically intractable organisms, the ability to engineer a bacterial genome in yeast will prove valuable in defining the minimal requirements for a viable organism. Perhaps in 2010 we may finally witness the emergence of a synthetic bacterium.

The possibility of creating synthetic life has, not surprisingly, raised security and bioethics concerns. Thus it is also a method, in 2010 and beyond, that society at large should watch.